This invention relates to the modification of laboratory animals for use in clinical studies and more specifically, to chronic catheterization of bile ducts of rats.
Tumor necrosis factor-xcex1 (TNFxcex1) is believed to be the primary mediator of endotoxin-induced hepatocellular dysfunction. This dysfunction results in decreased bile formation, a condition known as cholestasis. It has been shown that the endotoxin-induced TNFxcex1 response is dramatically attenuated by the surgical and nonsurgical stress associated with experimental protocols. In general, this condition, and others, can be evaluated in clinical studies by the use of chronically catheterized rats. Such rats have ligated common bile ducts, and a catheter connecting the bile duct to either a distal part of the bile duct or the intestine. In this use of such chronically catheterized rats, the bile duct will block or harbor bacterial colonies which adversely affect the study.
In the method of the subject invention, the common bile duct of a laboratory animal is cannulated but not ligated. The bile duct is left intact. Bile is siphoned by gravity from the catheter. In this manner, 100% of the bile is collected. The presence of the catheter does not alter hepatic function with respect to bile flow, bile acid flux, maximal indocyanine green biliary excretion, biliary gamma GT, or drug metabolism.